(1) Field of the Invention
This Invention concerns a DNA array and an analytical method of stress using said DNA array for the simple evaluation of degrees of stress. This Invention also concerns a method of evaluation of expression of gene groups related to certain diseases, not limiting to stress, by positioning oligonucleotides on substrate based on degree of correlation.
(2) Description of the Related Art
Increases in diseases associated with life style and atopic allergy are one of the factors that are responsible for the increase in today's medical burden to the nation. Reported also are increases in the numbers of suicides, lowering age of criminals and increases in patients with post-traumatic stress disorder (PTSD). Medical experts agree that stress play a role in background or life style-associated diseases, allergy, suicide, crime and PTSD.
Stress is defined as a reaction of the living body to sudden invasion, both as specific reaction to each invasion and as generic non-specific reaction, which has a fixed pattern regardless of the type of invasion. Stress-causing stimuli, or stressor, include abnormal temperature, burn, inflammation, immune reaction, noise, electric shock, ultraviolet light, bacterial toxin, bacteria, virus, operation, exercise, pain stimulus, physical restrain, hypoxia, hypoglycemia, ischemia, tests, interpersonal friction, deaths of relatives, loneliness, broken heart, despair, disappointment, social unrest, war, terrorism and earth quake. With advancement in knowledge of the maintenance mechanism of bodily homeostasis, it has become clear that there is a close relationship between abnormalities of the three major regulatory mechanisms of the body, the nerve, endocrine and immune system, and stress.
In conventional oligonucleotide array, it is decided first which genes are placed on chips, and then, according to the order, such as alphabetical order, designated to genes, genes are placed on a plate, such as a 96-well plate, using a spotter with several needles. In this method, although genes are lined up systematically, a step is required at the actual evaluation to confirm the positions of genes by consulting address information on files and images that show where and which genes are placed.
However, no medicophysiological diagnostic method has been developed by which the degree of stress can be evaluated objectively. For instance, blood concentrations of stress hormones, such as catecholamine and adrenocortical hormone, vary greatly among individuals and change with time. In other words, blood concentrations of stress hormones do not change uniformly in response to stress stimuli, and are known to be insufficient to be used for evaluation of degree of stress. In addition, it is extremely difficult to evaluate bodily reactions only by measuring these limited stress hormones because stress is the reaction of complex systems, requiring multilateral evaluations. Stress also is studied in the field of social psychology. Psychological tests in the form of interviews or questionnaires have been developed to evaluate degree of stress. However, it cannot be said that psychological tests substantiate sufficiently physiological reaction of the body. That is to say, currently, there scarcely are methods for objective evaluation of stress of individual persons. However, stress is an important phenomenon that is related to abnormalities of the automatic nervous system, endocrine and immune, gastric ulcer, acute lesions of gastric mucus, mental diseases and reproductive dysfunction. If it is possible to evaluate degree of stress readily at not only specialty medical organizations but also general-practitioners, health facilities at business and school and health screening centers, it is a useful measure, as feedback can be implemented in daily life at home, workplace and school. From that standpoint, development of diagnostic instruments is sought that can determine the degree of stress.
The objective of this Invention is to provide a diagnostic method, specifically, oligonucleotide array, by which degrees of stress can be determined readily and at low cost. In particular, this Invention aims at minimizing the number of DNA fragments placed on the array by specifying groups of genes, which are imperative in determination of degrees of stress, and at providing an array for stress analysis with high reproducibility and reliability. This Invention also aims at instant evaluation of the correlation between genes that are related a certain disease by devising regulations in how genes are arranged.